10 Dec 2014

Plant science is probably one of the least appreciated
fields of life sciences, and yet, perhaps no other research area has produced
as many technological advances beneficial for society. In an open letter
released last month, 21 out of the 27 most cited plant scientists in Europe pledged decision makers to back plant research, which they feel is currently
threatened by lack of funding and global public and political opposition to genetically
modified organisms (GMOs).

“In comparison for instance with biomedicine and
fields with technical applications, plant science is not well funded, and
that’s particularly true when it comes to funding from Horizon 2020”, says Stefan Jansson of Umea University (Sweden), who coordinated the
letter.

In the open letter the scientists recall the
fundamental role of curiosity-driven plant research for a sustainable society
and to “deepen our understanding of nature”, and they warn decision makers that
without their support—financial and political—the Horizon2020 goals to “tackle
societal challenges” and “to ensure Europe produces world-class science” will
not be met.

Besides asking for funding to be maintained or, if
possible, increased, they demand that plant scientists must be allowed to
perform field experiments with GM plant varieties, and that Europe must “promptly”
authorise new GM crops that have been found safe by the European Food Safe
Authority (EFSA).

They claim that in most European countries, “permits
to perform field experiments with transgenic plants are blocked, not on
scientific but on political grounds”. And the few field experiments that do go
ahead are often vandalised, wasting years of work and public funding. To
make matters worse, the scientists say in the letter, the ongoing de facto ban
on approvals for new GM plant varieties in Europe has not only been damaging
for applied plant science, but it has also increased the competitive advantage of
agrochemical corporation giants like Monsanto; publicly funded scientists and
small companies just don’t have the means to go through expensive, and
sometimes decade-long, approval procedures.

“Every
approval of a [GM plant] variety is enormously expensive, complicated and
unpredictable, so no one ever tries nowadays”, says Jansson.

GMOs in Europe

This opposition to GMOs can safely be called epidemic.
Lobbying by environmentalists and widespread popular resistance to GMOs has held
back the use of GM plants in agriculture globally, but only in Europe the
situation seems hopeless. A single GM plant is currently commercially
cultivated in the EU— the MON810 maze produced by Monsanto that carries
resistance to European corn borer, and which is cultivated in Spain, Portugal,
Czech Republic, Romania and Slovakia. A de facto ban on GMO approvals has kept GM plants
off the fields and out of our fridges for over 10 years. Environmental activists often
associate GM crops with the ‘big bad wolf’ agrochemical companies, but in fact
Monsanto and Syngenta have pulled out from the European market all together, so
effectively the only people affected by this ban are farmers and plant
scientists.

(March agains Monsanto, Vancouver, Canada, 2013. Credit: wikipedia)

“European agriculture is lagging behind when it comes
to development, yields and so on. So every year the rest of the world is improving
more than we’re doing here”, Jansson says “Unfortunately it’s because we’re not
allowed to use the right technologies”.

The extreme
position of France

This anti-GMO fever has changed the face of plant
research in some European countries. France is an extreme example. It’s a
national joke in France to say that all political parties, from far left to far
right, agree on one thing: they’re religiously against GMOs. The radical resistance
to GMOs in France began in the late 1990s amidst a growing anti-GMO mood that was
quickly spreading worldwide. Ironically, back in those days France was at the
forefront of the plant biotechnology field, and large consortium initiatives
such asGENIUS and GISBiotechnologiesVertes
(formerly known as
Génoplante) received generous public funding. In fact, the first ever field
experiment with a GM plant variety was performed in France in 1986, and for a
decade, France ranked second only to the United States in the number of these
experiments with GM crops, and they triggered no public protests. However, in
just a few years the number of field trials in France plunged from over a
thousand (in 1998) to only 48 (in 2004), and over half of these were eventually
destroyed by activists. So what happened?

As the mad-cow disease and beef hormones scandals
shocked the world in the mid 1990s, people began to become very sensitive about
what was in their food. And exactly around this time, the Monsanto’s Roundup
Ready soybeans controversy exploded. Not surprisingly, this promising new GM
technology didn’t go down that well with the public. As Greenpeace promptly launched
its first campaign against GMOs in 1996, a very influential French
environmental activist named José Bové started a strong anti-GMO movement that
conquered the French public opinion: from Parisian “bobos”, to journalists and
even scientists, everyone seemed to hate GMOs, and politicians just followed
the trend. The French Environmental Minister at the time, Corinne Lepage, began
introducing laws to ban cultivation of GM plant varieties, and all subsequent
governments, regardless of their political views, continued this anti-GMO
policy. Activists that destroyed GM crops and research labs were prosecuted but
got away with light sentences or amnesties. For instance, in 1999 protesters
led by Bové completely destroyed a greenhouse for experiments with GM plants at
CIRAD, a research centre for agriculture and sustained development in
Montpellier. After a long and highly publicised trial, Bové was prosecuted to
6-months in jail, but the then president Jacques Chirac eventually “pardoned”
four months of that sentence.

“They [the activists] are protected by the justice,
they’re not really condemned. The laws were relaxed by the courts. It’s easier
for these persons to get a meeting with the Minister of Research than for
scientists,” says Georges Pelletier, president of the Scientific Committee of
the French Association of Plant Biotechnology and former head of the Department
of Plant Physiology of INRA (French National Institute for Agricultural
Research).

Because of this strong public aversion to GMOs, and of
the heavy administrative burden and expensive greenhouses required for testing
GM varieties for agriculture, plant scientists in France have dropped their
arms and simply “lost hope”, says Pelletier. Now, they use GM technologies only
for basic research, and then adopt classical breeding methods to obtain the
desired plant variety, or otherwise they perform field experiments with GM
plants abroad.

“Nobody is growing GM crops outside anymore, after a
while you understand the message”, says Brigitte Courtois, a researcher at
CIRAD who is trying to obtain rice plants resistant to flooding by classical
breeding, and who got some of her plants destroyed by Bové. “My main worry is
that one day we’ll not be able to do any breeding because of this narrow vision.”

CIRAD and INRA, the largest public agricultural
research institutions in France, have reduced the use of GM technologies in applied
plant research to nearly zero. Once a leading country in plant biotechnology,
France plant scientists in public institutions are now forced to work almost
exclusively on fundamental research.

“The pressure on the scientists continues […] so in a
way these people are also more or less destroying the science. They put
pressure on the scientists hoping they will change their research”, Pelletier
says.

Communication
breakdown

(Credit: Acrylic Artist/Morguefile.com)

Since Monsanto’s Roundup Ready soybean scandal,
activists don’t seem to be able to distinguish the agro-industry sharks from
applied plant research, or in fact any plant research, so public and political
resistance to plant biotechnology and innovation persists, and plant scientists
suffer the collateral damage.

“I have stopped talking about [my work] with my
friends. Even educated friends with the same background in agronomy, they all
feel that there are other options, like organic farming […]. For me this is
associated with the fact that people have no contact with agriculture anymore,
they’re urban people who know nothing about how to grow a plant”, says
Courtois.

But in other countries, there are some signs that if
the public does listen to the researchers, they are more positive about the use
of GM technology to tackle societal problems. At Rothamsted Research (UK), one
of the world’s oldest agricultural research institutions, extensive information
about their field experiments with GMOs is available online, and researchers make
an effort to engage with the public to explain their research. The results
start to show: while a couple of years ago protesters attacked (but not
destroyed) a GM field trial at Rothamsted, the ongoing field experiment with Camina
plants that produce omega-3 oils hasn’t been at all targeted.

“When we discuss our work with the public the general
feedback is that the people are interested in what we are doing and more
positive towards the use of GM technology in trying to address research
questions and provide potential solutions to agriculture and food production
challenges”, said Rothamsted’s researchers in a statement to Lab Times.

It is difficult though for plant scientists to get the
message across to the public; if they’re not allowed to cultivate GM plants,
how can they show their benefits for agriculture and society? And if the public
doesn’t see those advantages, the lobbyists continue to put pressure on
politicians to ban GMOs. It’s a vicious circle.

“All the new environment-friendly varieties that
actually have been produced over the years, if they’re just in the drawers of
the scientists and never been used in practical agriculture, then its much
harder to convince society about the value of what we’re doing,” says Jansson.

Politics vs
science

The date for the release of the open letter, at the
end of October, was chosen carefully. The new European Commissioner for Public
Heath and Food Safety, Vytenis Andriukaitis, took office on the 1st
of November, and just a few days later the European Parliament voted on a Commission’s
proposal to give power to individual member states (MS) to ban GMOs in their
territory.

This proposal was initially meant to be a compromise
to unblock the over 10-year-long gridlock on GMO authorisations. Currently, any
GMO approval in the European Union (EU) first needs to go through a thorough science-based
evaluation by EFSA, and then the Commission drafts a proposal to either ban or
authorise the new GMO according to EFSA’s recommendation. The proposal finally
goes to the Standing Commission—made of politicians representing EU governments
and public authorities—and they have the final say. If nine or more countries
are against the Commission’s proposal, the approval is blocked. This has
happened systematically for over a decade.

“When it comes to pharmaceutical industries, for
instance, it’s not the politicians that make the evaluations whether the drug
is dangerous or has side-effects or not, it’s the scientific body that does
that”, says Jansson.

Anti-GMO countries like France have stalled the system
by using spurious scientific arguments to ban GMO approvals, and applicants are
either forced to spend years on end doing more and more safety tests, or they
have to go into long and expensive legal battles to overturn the Commission’s
decision (or lack of thereof). Inevitably, companies trying to commercialise
their GM plant variety in Europe give up, while publicly funded researchers
don’t even try.

This de facto ban has worked well for anti-GMO
countries so far, but ironically, because of the countless scientific studies
they’ve imposed, a huge amount of scientific evidence has accumulated showing that
GMOs don’t pose any risk for human health or the environment. Anti-GMO
countries are running out of arguments.

As a result, in an unprecedented move, thirteen
countries formally asked the Commission to give MS the “flexibility” to ban EU-authorised
GMO crops in their territory. Even though this would in theory go against the
single market principle, in June 2014 the Commission approved a compromise proposal
granting that request, but preventing MS from banning EU-authorised crops based
on health or environmental grounds. This was a painful and much-negotiated compromise
that could have worked. However, amendments introduced to the proposal by
lobbyists will effectively give countries legal grounds to ban GMOs on reasons
such as “environmental policy, town and country planning, land use,
agricultural policy, public policy, or possible socio-economic impacts, GMO
contamination of other products, persistent scientific uncertainty, development
of pesticide resistance amongst weeds and pests, invasiveness, the persistence
of a GMO variety in the environment or a lack of data on the potential negative
impacts of a variety”, MEPs say in a press release. So pretty much any reason
will do.

The Commission’s amended proposal was approved by the
European Parliament in November. The decision is not final yet, but the future
for GMOs in Europe seems bleak.

“The amendments that give MS the ability to challenge
cultivation on grounds of safety are worrying because they undermine the risk
assessment performed by EFSA” Rothamsted researchers voice their concern in a statement to Lab
Times. “Potentially, it will also make it harder for MS who do not want to
opt-out to justify to their consumers when neighbouring MS are using safety as
a reason to ban”.

The worry is that pro-GMO countries won’t be able to
cultivate EU-authorised GM crops in their country because activists can now say
“If that country banned this crop on safety grounds, it must mean it’s unsafe”,
and this will put even more pressure on politicians to ban GMOs. EFSA’s
science-based evaluation will lose weight on GMO approvals; the power will lie merely
on politicians, and science will have little impact on future decisions to
authorise or ban GM crops in Europe.

Seeds for the
future

The open letter has so far not received any response
from the European Commissioner, but it got extensive media coverage and
excellent feedback from the research community, except in France, where
researchers seem to prefer to remain quiet.

“The letter was addressed to two French scientists
amongst the best in Europe and they didn’t want to sign. One of them because of
the question of GMOs and application was inserted in the letter, so he didn’t
want to sign. The other never replied”, reveals Pelletier.

So what’s the future for plant science in Europe?

Jansson says “It won’t disappear but it won’t
flourish either. Maybe, in 10 years, there will be fewer plant scientists and
they will be a little less useful for society.”

28 Oct 2014

Just like for married couples, communication is
fundamental for cells. When an embryo is developing, its cells need to tell one
another who and where they are, so every tissue and organ grows in
the right place and at the right time. Our neurons are constantly talking to
each other to control our thoughts, feelings and behaviours. Even single-cell
organisms like bacteria can exchange information to decide, for example, how
many times they should multiply.

But how do cells communicate? Scientists have a
good understanding of the key proteins involved in cell communication, or cell
signalling. Typically, a cell sends out a chemical signal (or electrical, in
the case of neurons) that sticks to a specific receptor protein on the surface
of the neighbouring cells. We then say the receptor is ‘activated’, because it
can trigger a cascade of molecular events that ultimately leads to a cellular
response. For instance, the cell might start moving in a particular direction, or a specific
gene gets translated into protein.

There is, however, quite a lot we still don’t know
about cell signalling. What would happen if we could activate a receptor only at
the tip of a moving cell? Would the cell change the direction of migration? And
what if we could activate a receptor repeatedly, or at different time intervals?
Would the cell responses be different? Questions like these have been bugging
scientists for decades, but they simply lacked the tools to address them.

Now, a research team led by Harald Janovjak at the
Institute of Science and Technology (Austria) has developed a new method to
study the fine temporal and spatial regulation of cell signalling using
proteins activated by light. This work opens the way for the development of
powerful approaches to manipulate cell behaviour in health and disease.

Human cells illuminated in a pattern depicting the letters IST. The cells carry a reporter gene that 'glows' when it is triggered with light-activated receptor tyrosine kinases (Credit: Medical University of Vienna).

The
optogenetics revolution

Scientists have been using engineered light-activated
proteins to manipulate cell activity for about a decade or so, a technique that
has been named ‘optogenetics’. The first light-activated proteins, or photoreceptors,
applied in optogenetics belonged to the microbial opsin family. These opsin
photoreceptors are useful because they can move ions across cell membranes in
response to light, a process similar to what triggers neuron activation. In
these initial studies, channelrhodopsins (a type of opsin photoreceptor) were removed from algae and inserted
into particular neuronal cell types in mice. Upon exposure to light, the
neurons containing these proteins started to fire, and depending on which
neurons were activated in this way, a different behaviour was observed in the
mice; in one study, the mice’s levels of anxiety increased, and in another they
started going round in circles.

The reason why optogenetics has been coined a ‘revolutionary
technique’ (and why it is tipped for a Nobel prize) is that it allows scientists
to control the activity of particular cell types or proteins with an
unprecedented level of precision, both in a temporal and spatial manner. And
this, sure enough, comes very handy for cell signalling research. It is a bit
complicated though, to build optogenetic tools for that purpose.

“The main challenges are the same as for many
engineering problems. For example, you want the signalling receptor to be
completely inactive in the “OFF” condition (no light), and to be as much active
as if the natural chemical signal is added in the “ON” condition (light),” says Janovjak.

This fine level of receptor manipulation is very hard
to achieve with conventional optogenetics tools, so Janovjak and
colleagues decided to build signalling receptors activated by light from
scratch, by taking bits and pieces from several proteins and then sticking them
together.

They focused on cell-surface receptors of the receptor
tyrosine kinase (RTK) family, which sense growth factors and hormones and have
been involved in a variety of cellular processes. When an RTK receptor is
activated by a chemical signal, let’s say a growth factor, it attaches to
another receptor in what is called ‘dimerisation’. It is this contact between
two RTK receptor molecules that triggers the molecular events leading to a cell
response, or in other words, that activates RTK signalling. Janovjak and
colleagues knew this, so they looked in bacteria, fungi and plants for proteins
that dimerise in response to light, and then fused them to an RTK receptor
skeleton. In theory, these engineered RTK receptors should dimerise—and
therefore become activated—upon light exposure.

“We were quite beautifully able to do this. In our
study cancer cells with RTKs under optical control quantitatively respond to
light and the growth factor! This is nothing short of amazing and the basis for
all future work by us and others,” says Janovjak.

Manipulating
cell signalling with light

The team showed that when engineered RTKs are inserted
into several cell types, including cancer cells, they can be efficiently
activated by light and induce the predicted cell response very quickly and
within a tiny spatial range.

Morgan Huse, an expert on cell signalling at the Sloan
Kettering Institute (US) says “This study represents the first time that
homodimerising [light-activated] protein domains have been used to activate RTK
signalling. The results are quite significant.”

These new optogenetic tools will be invaluable for
understanding cell signalling, and could also be adapted to study other
cellular processes. In the future, Janovjak’s team will use these tools to
investigate regeneration.

“Our research will focus on regeneration. In essence,
growth factors are known to be efficacious in disease animal models, including
diabetes and Parkinson’s disease. However, delivery of these growth factors is
a real issue because they can induce side effects like (but not limited to)
cancer, and growth factors often can’t reach the desired cells (for example in
the brain). Maybe optogenetics can help”.

22 Sep 2014

I recently spoke with Nobel laureate Sir Tim Hunt about the current research scene in Europe in an interview for Lab Times. We discussed topics such as research funding, gender inequality in academia and the publishing system. Below is a summary of his career and the full interview.

Sir Tim Hunt started his research career
in 1964 at the University of Cambridge (UK) working on haemoglobulin synthesis
under the supervision of Asher Korner. After obtaining his PhD in 1968, he
spent a few years at the Albert Einstein College of Medicine in New York (US)
working with Irving London, until he returned to Cambridge to teach and establish
his independent research career studying translational control. In the late
1970s, he began teaching a summer course at the Marine Biological Laboratory,
Woods Hole (US), where he began working with sea urchin and clam eggs. These experiments
eventually led to the discovery of cyclins, a family of regulatory proteins
that partner with cyclin-depent kinases (CDKs) to control the transition
between cell cycle phases. For this breakthrough Hunt was awarded the Nobel
Prize in Physiology or Medicine in 2001, together with Lee Hartwell and Paul
Nurse for their work on CDKs in yeast. In 1990, Hunt moved his laboratory
to the Clare Hall Laboratories at Imperial Cancer Research Fund (now London
Research Institute/Cancer Research UK) where he carried out pioneering research
on cyclins and cell cycle control until his recent retirement. He is a former Chair
of the European Molecular Biology Organisation (EMBO) council, and currently
member of the Scientific Council of the European Research Council (ERC), the
Advisory Council for the Campaign for Science and Engineering (CaSE) and of
the Selection Committee for the Shaw Prize in Life Science and Medicine.

You have recently
retired from a long and prolific research career. How different is it to pursue
a research career now, compared to when you started, or even just a couple of
decades ago?

Hunt: I always like to joke that I am glad
that I am not 20 something years old today, because I think it is much harder
than when we started. When I started as a PhD student in 1964 our department
didn’t have a Xerox machine, there were no calculators, you had to go to the
library to read things and it was virtually impossible to analyse individual
proteins because the SDS gel had not yet been invented. The tools were very
blunt and the questions you could ask were corresponding limited; now the two
are exceedingly sharp and the analytical procedures are absolutely awesome. […]
When you look back at the papers of that era they were pretty simple, easier to
understand in many cases. There was only so much you could do. I am appalled
sometimes at some papers today; they are so data heavy, and I don’t think that
makes them better papers. […] In terms of publication there is just much more
competition these days, because the biosciences have been so successful; they
consume about 2% of the growth national product in the US and the result is
that there are thousands of competing young scientists. My generation is just
on the point of retirement, and in the meantime we have all trained dozens of
doctoral students and postdocs, each of which has trained their own students
and postdocs, so this exponential growth is what caused all the problems, I
would say.

And where do you think all this is heading?

Hunt: I really don’t know… Somewhere between
1990 and 2000 many of the outstanding problems of cellular, molecular and
developmental biology were effectively solved. You do kind of wonder: how many
really important problems are there in biology that remain? Of course there are
hundreds of details but the last great frontier is how the brain works, there
you have a very primitive partial understand of most of it. […] It is a pretty
difficult problem.

Is the European Union currently taking the right measures to move European
science forward?

Hunt: The old investigator-led grants are
excellent and much better that top-down collaborative network grants, which are
quite good fun but I don’t think it is a terribly good mechanism to hunt for
the best science because the people aren’t really working together. When you
really work with somebody you see them everyday, and here the idea is that you
see one another once a year, or perhaps four times a year, it just doesn’t
work. There are projects that might work, like these huge projects to sequence
the human genome, the big science, but mostly I think that biology is still
pretty small science that has to be carried out by committed individuals
focusing on particular problems. I don’t know very many things that require
that kind of effort.

What are the strengths and pitfalls of the European research community, when
compared, for example, with research in the US?

Hunt: I think things have improved
tremendously in Europe in the last few years. For example, in my field, the
European Molecular Biology Laboratory (EMBL) has trained lots of people, not
only in how to do science, but also on how to manage science and how to choose
scientists. […] I believe very much in giving power to the young and not
putting them under. I was given full autonomy and authority at a very young
age, at 27 years old. I wasn’t running my own lab, I had friends around to help
and I liked that. There is much more internationalization in Europe, good
practice [of science] is much more diffused throughout. In the former communist
countries, Poland, Bulgaria and places like that, they still have a long way to
go but it is difficult to feed because any new talent that arises, very quickly
migrates abroad. At the ERC we think about that a lot but we haven’t really
taken steps to deal with it because it is against our principles. We say
excellence only and that rules most of those people out, and it is
understandable, they don’t have a good science base, and it is hard to see how
they can build one.

What do you think of big science
prizes like the Breakthrough Prize? Some people claim that junior scientists should receive this type of prize instead of established scientists.

Hunt: I
don’t know to be honest. You have to find a compromise. If you are a granting
agency, you really do need to try to identify people who are successful and
clever, and that will make good use of the money. There are a lot of funding
agencies and in the past you feel that every person had to get a little piece
of the cake, and in general, that meant that the food is spread too thinly. So
I think that a bit of concentration is a good idea, but that then raises the
question: how do you identify the good people? That is when the problems begin,
because now we start talking about impact factor and things like that and
everybody knows there are problems with that but nobody has found a
satisfactory solution. We are good at judging science retrospectively but we
are not good at judging science prospectively, because the future is always
very hard to predict. The ERC does the best it can. We like to keep things very
simple and in judging grant applications you give half the marks to track
record of the applicant and half the marks to the project they propose. I think
that is a pretty good ratio. You can’t just give money to people who have been
successful in the past and say ‘do whatever you’d like’, I don’t think that
sort of view is responsible although in some cases it will be fine. And
likewise people can propose very fancy and clever research projects but when
you look at their productivity you see that they are much better at writing
grants than actually carrying out research. Somewhere between those two
extremes lies the compromise.

How can we change the way scientists
(and science) are perceived by the public?

Hunt: I
don’t know, I think that is a very difficult question to answer. People always
say that scientists must be encouraged to go out and explain what they are
doing. I’m all for that, I try to do a little bit, I go and talk in schools and
so forth. But nothing never really comes close to the experience of actually
doing science, which is usually a rather peculiar random walk, mostly failure
and the occasional few successes. But it doesn’t really explain why it is so
wonderful and such good fun to do because in order to understand it you have to
usually have first done a PhD in the subject and most people haven’t. I would
find it difficult to explain to a quantum mechanics expert what I was doing and
why I thought it was interesting. […] Science is really just a way of finding
things out. You pursue a lot of false clues, you get misled and misinterpret
things. And that is very hard to convey and unfortunately I think the teaching
of science in school is very delusive…. They make it sound that there are some
geniuses out there that figured everything out and then wrote it down in textbooks.
And all you have to do is learn what it says in the textbooks and you will be a
brilliant scientist, but we all know that textbooks are actually wrong in lots
of places. And the alternative to that of course is: ok we won’t teach the kids
what is known, we will let them find it all out for themselves. But if you have
to find everything out for yourself it takes an awfully long time to discover
anything. It is really important to have practical experience, but it is very
difficult to give people practical experience of what it is really like to be
pursuing a real live problem.

Do you think scientists are
pressured to focus their research on ‘hot’ topics, like cancer or neuroscience?

Hunt: I
think they are. It is the money issue; people tend to migrate in that direction
because they have no choice. I don’t think it is a very sensible way to spend
the money. I am a tremendous believer in fundamental research. When I look at
the great breakthroughs, like the discovery of penicillin, that wasn’t produced
by doctors wanting to make antibiotics, none of them realised it was possible.
It was a tiny handful of basic researchers who were curious and figured out how
to do it. I think this emphasis on translation research is very foolish,
because it implies that we know everything that we need to know, and that is
not true obviously. A good example is the case of gene therapy, which is much
needed to treat genetic diseases and it doesn’t work very well because much
more biological engineering is required. I think most biological fields are
well populated, and if a breakthrough occurs they won’t fail to exploit them.

How would you explain to someone
in one sentence that it is important to fund and encourage more basic research?

Hunt: I
wouldn’t know how to begin! I think it is extremely difficult to justify
because what you are really saying is ‘just pay me to have more fun’ and that
works much better than paying me to do something I have no clue how to do.

In your opinion, why are women
still under-represented in senior positions in academia and funding bodies?

Hunt: I’m
not sure there is really a problem actually. People just look at the
statistics. I dare myself think there is any discrimination, either for or
against men or women. I think people are really good at selecting good
scientists but I must admit the inequalities in the outcomes, especially at the
higher end, are quite staggering. And I have no idea what the reasons are. One
should start asking why women being underrepresented in senior positions is
such a big problem. Is this actually a bad thing? It is not immediately obvious
for me that… is this bad for women? Or bad for science? Or bad for society? I
don’t know, it clearly upsets people a lot.

What
research area excites you at the moment?

Hunt: I
am very excited by stem cell biology. I think the advances that have been made
are just fantastic and I really hope that is something that will lead to people
growing pancreas in a test tube and use them to cure diabetes, for example. I
think that those advances have been absolutely spectacular, very, very
interesting.

16 May 2014

Water bears, or tardigrades, are harmless microscopic
animals. Yet, despite their endearing bear-like appearance, tardigrades are the
hardest animals to kill on Earth. And boy, many have tried.Tardigrades are chubby eight-legged animals, no longer than the head of a pin, related to velvet worms and also arthropodes, a large family including insects, spiders and crustaceans. They can be found anywhere where there’s water, but they prefer to live in damp moss and lichens. These tough creatures can survive boiling temperatures up to
125˚C* and freezing temperatures so extreme (-272˚C!) they can only be
artificially created in a laboratory. They can also survive astonishing amounts
of radiation with no apparent damage to their DNA, extremely high pressures,
and, unlike any other earthly creature, tardigrades can hang out for a few
minutes in the vacuum of space and come back alive to tell the story.

So what’s their secret? Tardigrades have the amazing
ability to reversibly slow down their metabolism to nearly a halt (less than
0,01% of their normal metabolic rate) in response to a change in their
environment—a process called cryptobiosis. Other organisms can do it—nematodes,
rotifers, brine shrimp—but not nearly as spectacularly as tardigrades. It is estimated that they can lose up to 99% of their water content, and enter a so-called
‘tun’ stage that protects them against harsh environmental conditions. Yet, if
you rehydrate these tuns, the animals will quickly return to their normal
selves—moving about, growing and having babies, as you do when you’re a
tardigrade (watch movie below).

Scientists grow tardigrades in the lab (and sometimes in space) to
study cryptobiosis. Understanding how tardigrades survive extreme dehydration during
the tun stage could help developing better techniques for dry
preservation of biological material, for example.In a recent study, Marcus Frohme and colleagues from the Technical
University of Applied Sciences in Wildau (Germany) compared differences in gene expression between happy, dehydrating, tun stage and rehydrated tardigrades.
The idea was to search for the genes that are more, or less active in each of
these metabolic states, which could give some clues as to how the tardigrades’
cells cope with severe dehydration. The researchers grew four groups of animals in the lab under different conditions (from moist to dry) and then smashed them up to chemically extract mRNA molecules (copies of DNA that will be
translated into proteins) from their cells. They then sequenced and quantified these molecules, and finally analysed the huge amount of data
using a powerful computer software.The team found that in
the dehydration stages, genes involved in cell division and growth were less
active, but genes encoding for proteins that protect or repair cellular
components, such as heat-shock proteins, were highly expressed. These results confirm previous research, but some preliminary
data in Frohme's study also suggest that several genes involved in DNA repair are more active
in the rehydration stage than in the dehydration stage. The authors propose
that tardigrades adopt a dual strategy combining mechanisms of protection (during dehydrating stages) and recovery (during rehydration stages) to survive desiccation.

18 Feb 2014

3D printing is in fashion. Clothes, prosthetic limbs, guns
and even pizza, you name it—just about anything can be printed these days. Even
living cells.

Bioprinting is an emerging technology that promises to
revolutionise the field of regenerative medicine. The idea is simple: you load
a printer cartridge with cells removed from a patient or grown in the lab, and
then print a brand new tissue or organ ready for transplantation.
Alternatively, you could print healthy tissue directly onto a patient’s wound
in the operating room. For now, scientists and biotech companies have managed to
print several cell types, and there has been some progress in making cartilage,
skin and heart muscle tissue. Printed tissues like these could be invaluable
for drug testing in preclinical studies and for regenerative medicine. Imagine
if we could replace damaged brain tissue in people suffering from
neurodegenerative diseases like Alzheimers, or treat blindness with transplanted
eye tissue. But how does bioprinting work?

By a lucky coincidence, the size of the nozzles of
inkjet printers is roughly the same of an average animal cell, so scientists
can use or adapt commercial printers for bioprinting. Just like a conventional
3D printer, which creates objects by laying down liquefied material (like
plastic, metal or even chocolate) in layers, bioprinters work by spitting out
cell after cell onto a surface to, in theory, build a 3D-shaped living tissue. But
there is a caveat. Some cells are not happy to be squeezed through a printhead,
like neural cells for example, which have a limited ability to survive and grow
in culture.

Barbara Lorber and colleagues pushed a gel containing the cells
through a piezoelectric inkjet printer and then tried to grow them in culture
to test their survival rate. Piezoelectric printers are not commonly used for
bioprinting because they use an electrical pulse to eject the ink drops, and
this was thought to break cell membranes. But this is not what the team found. The
large majority of printed ganglion and glial cells were able to survive and
grow in culture. They also seemed to retain their function—glial cells released
growth-promoting molecules, and in turn ganglion cells responded to these
signals by growing more of the tiny processes that carry messages to neurons.

In recent years, stem cells transplants and electronic
retina implants were shown to partially restore sight in patients with retinal
degeneration, but these improvements were modest. Although preliminary, the new
results by the Cambridge team provide the proof-of-principle that the
production of functional retinal tissue by bioprinting could one day become a
reality.